The FAST-MAS initiative will focus will be on novel molecular and clinical targets that may cut across diagnostic categories within the mood and anxiety spectrum, and may also be relevant to other mental disorders. Mood and anxiety spectrum disorders, as represented in the DSM-IV-TR, are among the most common and serious disorders treated by mental health practitioners. These include major depressive disorder; dysthymic disorder (a chronic, mild depression); and bipolar disorder (also called manic depression). There are a wide variety of anxiety disorders, including generalized anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and special phobias. This initiative seeks to expeditiously test and analyze novel interventions (i.e., compounds) and their molecular and/or clinical targets for treating clinical dimensions of psychopathology (e.g., anhedonia, cognitive function, social engagement) associated with traditional mood and anxiety spectrum disorders. Of particular interest are features of mood and anxiety spectrum disorders as described in the current DSM-IV-TR diagnostic entities, but not typically identified as the primary target of current clinical therapeutics. As described above, there is interest in the study of mechanisms that cut across traditional disorder categories and where relevant mechanisms and clinical targets are assessed directly rather than being inferred through assignment of a particular diagnosis. The outcome of this initiative is expected to lead to enhanced understanding of specific target engagement by such novel interventions, leading to development of innovative treatment approaches for clinical dimensions of psychopathology associated with traditional mood and anxiety spectrum disorders. In this context, novel interventions (i.e., compounds) may refer either to new chemical entities (NCEs) or to compounds that are being considered for re-purposing from other indications. Testing of compounds that have been FDA-approved for other indications (re-purposing) is of interest if recent basic research discoveries suggest that the compound(s) have the potential to affect a biological mechanism contributing to mental disorders and that has previously been untested in clinical studies. Compounds acting on molecular targets that replicate those of currently marketed psychiatric pharmaceuticals are not of interest for this contract. The primary objective of this contract is to expeditiously perform small-scale Phase I and/or Phase IIa clinical trials (e.g., First In Human (FIH), Proof of Clinical Mechanism (POCM), Proof of Concept (POC)) to demonstrate target engagement, safety, and early signs of efficacy of such promising compounds in healthy subjects and/or a well-characterized cohort of patients with clinical dimensions of psychopathology associated with traditional mood and anxiety spectrum disorders. Depending on pilot data available for compounds selected for testing, each trial may be a single-site or multisite study with a number of subjects adequate to successfully address the primary aims (e.g., pharmacologic dose range, safety in humans, molecular and/or clinical target engagement, potential biomarkers, biological effects, early signs of efficacy) and inform a judgment whether the particular compound warrants further evaluation.